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Differential Effects on Intestinal Adaptation Following Exogenous Glucagon-Like Peptide 2 Therapy With and Without Enteral Nutrition in Neonatal Short Bowel Syndrome [Formula: see text].

Authors
  • Lim, David W1
  • Diané, Abdoulaye2
  • Muto, Mitsuru3
  • Vine, Donna F2
  • Nation, Patrick N4
  • Wizzard, Pamela R3
  • Sigalet, David L5
  • Bigam, David L1
  • Pencharz, Paul B6
  • Turner, Justine M2, 3
  • Wales, Paul W1, 3, 7
  • 1 1 Department of Surgery, University of Alberta, Edmonton, Alberta, Canada. , (Canada)
  • 2 2 Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada. , (Canada)
  • 3 3 Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. , (Canada)
  • 4 4 Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada. , (Canada)
  • 5 5 Department of Surgery, University of Calgary, Calgary, Alberta, Canada. , (Canada)
  • 6 6 Department of Nutritional Sciences and Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada. , (Canada)
  • 7 7 Department of Surgery, Hospital for Sick Children & University of Toronto, Toronto, Ontario, Canada. , (Canada)
Type
Published Article
Journal
JPEN. Journal of parenteral and enteral nutrition
Publication Date
Feb 01, 2017
Volume
41
Issue
2
Pages
156–170
Identifiers
DOI: 10.1177/0148607116665812
PMID: 27660290
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

We aim to study the efficacy of exogenously administered glucagon-like peptide 2 (GLP-2) on intestinal adaptation in 2 preclinical models of neonatal short bowel syndrome (SBS) according to remnant intestinal anatomy, with and without ileum. Furthermore, we aim to determine if this adaptive effect was potentiated with enteral nutrition (EN). Neonatal piglets were block-randomized to 75% mid-intestinal (JI group, retains ileum) or distal-intestinal (JC group, has no ileum) resection or no resection (sham control) and GLP-2 treatment (11 nmol/kg/d) or saline control for 7 days. Piglets received nutrition support, either 100% parenteral nutrition (PN; 0% EN, n = 32 in total) or 80% PN + 40% EN (n = 28 in total). Adaptation was assessed by morphological and histological changes, as well as RT quantitative polymerase chain reaction of nutrient transporters and tight junctional proteins and fat absorption. Data are analyzed by 3-way analysis of variance (ANOVA) and 2-way ANOVA per EN level. GLP-2 treatment lengthened villi, deepened crypts, and improved intestinal weight in the remnant intestine of JC piglets. EN was a more potent adaptive stimulus for JI piglets. Small intestinal lengthening occurred only in the JI group, when given EN. There was no difference in total fat absorption and messenger RNA expression of nutrient transporters and tight junctional proteins. GLP-2 administration augmented structural adaptation in JC piglets with distal intestinal resection. Given JI anatomy, further stimulation by GLP-2 treatment over innate adaptation and stimulation by EN was modest and restricted to ileum. The differential effect of GLP-2 in neonatal SBS, depending on remnant anatomy, has important implications for clinical translation and planning of clinical trials.

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